Int J Biochem Mol Biol 2011;2(1):31-38
Original Article
The Role of dileucine in the expression and function of human organic anion transporter
1 (hOAT1)
Qiang Zhang, Jinwei Wu, Guofeng You
Department of Pharmaceutics, Rutgers, the State University of New Jersey, and §Department of Pharmacology, UMDNJ-Robert Wood Johnson
Medical School, Piscataway, NJ 08854
Received October 13, 2010; accepted November 11, 2010; Epub November 20, 2010; published February 15, 2011
Abstract: Human organic anion transporter hOAT1 plays a critical role in the body disposition of environmental toxins and clinically important
drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. In the current study, we
investigated the role of dileucine (LL6) at the amino terminus of hOAT1 in the expression and function of the transporter. We substituted LL6
with alanine (A) simultaneously. The resulting mutant transporter LL6AA showed no transport activity due to its complete loss of expression at
the cell surface. Such loss of surface expression of LL6AA was consistent with a complete loss of an 80 kDa surface-resident mature form and
a dramatic decrease in a 60 kDa endoplasmic reticulum (ER)-resident immature form of the mutant transporter in the total cell lysates.
Treatment of LL6AA-expressing cells with proteasomal inhibitor resulted in the significant increase in the endoplasmic reticulum (ER)-resident
immature form of hOAT1, but not its surface-resident mature form, whereas treatment of these cells with lysosomal inhibitor had no effect on
the expression of the mutant transporters, suggesting that the mutant transporter was degraded through proteasomal pathway. Furthermore,
treatment of LL6AA-expressing cells with sodium 4-phenylbutyrate (4PBA) and glycerol, two chemical chaperones, could not promote the exit of
the immature form of the mutant transporter from the ER. Our data suggest that LL6 is critical for the stability and ER export of hOAT1.
(IJBMB1010001).
Keywords: Dileucine, organic anion transporter, drug transport
Full Text PDF
Address all correspondence to:
Guofeng You, PhD
Dept. of Pharmaceutics
Rutgers, the State University of New Jersey
160 Frelinghuysen Road, Piscataway, NJ 08854, USA
Tel: 732-445-3831 x 218
E-mail: gyou@rci.rutgers.edu
Original Article
The Role of dileucine in the expression and function of human organic anion transporter
1 (hOAT1)
Qiang Zhang, Jinwei Wu, Guofeng You
Department of Pharmaceutics, Rutgers, the State University of New Jersey, and §Department of Pharmacology, UMDNJ-Robert Wood Johnson
Medical School, Piscataway, NJ 08854
Received October 13, 2010; accepted November 11, 2010; Epub November 20, 2010; published February 15, 2011
Abstract: Human organic anion transporter hOAT1 plays a critical role in the body disposition of environmental toxins and clinically important
drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. In the current study, we
investigated the role of dileucine (LL6) at the amino terminus of hOAT1 in the expression and function of the transporter. We substituted LL6
with alanine (A) simultaneously. The resulting mutant transporter LL6AA showed no transport activity due to its complete loss of expression at
the cell surface. Such loss of surface expression of LL6AA was consistent with a complete loss of an 80 kDa surface-resident mature form and
a dramatic decrease in a 60 kDa endoplasmic reticulum (ER)-resident immature form of the mutant transporter in the total cell lysates.
Treatment of LL6AA-expressing cells with proteasomal inhibitor resulted in the significant increase in the endoplasmic reticulum (ER)-resident
immature form of hOAT1, but not its surface-resident mature form, whereas treatment of these cells with lysosomal inhibitor had no effect on
the expression of the mutant transporters, suggesting that the mutant transporter was degraded through proteasomal pathway. Furthermore,
treatment of LL6AA-expressing cells with sodium 4-phenylbutyrate (4PBA) and glycerol, two chemical chaperones, could not promote the exit of
the immature form of the mutant transporter from the ER. Our data suggest that LL6 is critical for the stability and ER export of hOAT1.
(IJBMB1010001).
Keywords: Dileucine, organic anion transporter, drug transport
Full Text PDF
Address all correspondence to:
Guofeng You, PhD
Dept. of Pharmaceutics
Rutgers, the State University of New Jersey
160 Frelinghuysen Road, Piscataway, NJ 08854, USA
Tel: 732-445-3831 x 218
E-mail: gyou@rci.rutgers.edu
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